The proposed research is aimed at determining how the brain mechanisms controlling daily rhythms differ in animals that are active during the day compared to animals that are active at night. This proposal focuses on comparisons between the nocturnal lab rat and a diurnal rodent, the unstriped Nile grass rat. The research will focus primarily on a region of the brain that includes the suprachiasmatic nucleus (SCN), which is the site of the primary circadian "clock," and on neural tissue that surrounds this nucleus. The latter is referred to as the "peri-SCN" region, and it exhibits dramatically different rhythms in the diurnal grass rat compared to the nocturnal lab rat. The peri-SCN region will serve as a powerful model with which to characterize mechanisms that can lead to a reversal in rhythms exhibited by diurnal compared to nocturnal animals. The first Specific Aim is to evaluate the interaction between internal and external mechanisms that influence the peri-SCN rhythm in nocturnal and diurnal rodents. The second Specific Aim is to evaluate inputs to this region that could cause it to function differently in nocturnal and diurnal animals. The third Specific Aim is to elucidate the pathways through which the peri-SCN region could influence rhythms in sleep and body temperature. The fourth Specific Aim is to characterize, in the diurnal species, the molecular mechanisms underlying the "clock," and molecular pathways through which temporal information is transmitted from the clock to the behavioral and physiological systems it controls. The project has important implications for human health. One reason is simply that humans are predominantly diurnal, and the vast majority of medical research is conducted in nocturnal rodents. Somehow, somewhere in the brain, the temporal signals are reversed in day and night-active mammals, which makes it difficult to know whether lessons learned from nocturnal rodents truly apply to humans. A second medically important feature of the proposed work is that many humans have serious problems adapting their internal rhythms to the environment around them, which can lead to serious problems in life in general and on the job in particular.